All humans age, though the rate of aging is highly variable and likely influenced by one's genetic composition; our cells accumulate damage over time, and this damage can lead to increased disease susceptibility, decreased ability to respond to injury, reduction in sensory systems, among many other detrimental changes. While not necessarily deadly on their own, they lead to a greatly increased risk of death. In order to begin the clinical work in reducing the effects of aging, research must first elucidate the biochemical interactions causing such effects. This project will identify and describe pathways containing conserved longevity-related protein synthesis genes using the model organism, C. elegans. The nematode C. elegans is an excellent model for aging due to its short lifespan, small number of cells, ease of genetic manipulation, and large fraction (>80%) of conserved genes. The reduced expression of protein synthesis genes post-developmentally increases worm lifespan, even up to 50% higher, but the reasons for this lifespan increase are unknown. It has recently been described that reducing protein synthesis cause developmental arrest if given during the larval stage. Given this connection, and multiple previous studies describing similar longevity-related antagonistic pleiotropy, we seek to characterize the protein synthesis pathways involved in both phenotypes; this includes testing the hypothesis that these two phenotypes may use the same pathway as we have recently determined both of these states share a stress resistance phenotype (a metric of increased healthspan). Aim 1 will compile a list of deregulated genes via RNA-seq when worms undergo arrest or longevity in response to reduced protein synthesis. Using this list, and three previously-identified genes that can control the arrest phenotype, we will characterize their spatiotemporal expression patterns, using GFP-bound promoters, and how they correlate with the longevity, arrest, and stress resistance phenotypes. Finally, we will determine if rescuing wild type expression levels of these deregulated genes rescues any of the same phenotypes, indicating their importance in that response. Aim 2 will determine the effects of reducing protein synthesis in a tissue-specific manner (hypodermal, intestinal, muscular, or neuronal) using tissue-specific RNAi strains, which will identify where in the worm the longevity pathway is taking place, including revealing how the signaling and cell-cell crosstalk interacts between cell types to confer longevity, arrest, and stress resistance. The second part of Aim 2 involves coalescing information from our spatiotemporal analysis and tissue-specific studies in order to rescue genes found to be important in conferring these survival-promoting phenotypes in order to determine their importance on a cell or tissue-based level. The description of these protein synthesis genes, particularly in relation to their physiological effects, discovered pathways, and correlation with arrest states and stress resistance, will establish a better connection between enhanced longevity and how that longevity is conferred in order to enable the eventual treatment of aging-related ailments and disease.